Pteridines are known from the prior art as active substances with an antiproliferative activity. See, e.g., Merz et al., Journal of Medicinal Chemistry 1998, 41, 4733-4743 (the preparation of 7-benzylamino-6-chloro-2-piperazino-4-pyrrolidinopteridine and derivatives thereof which are free from positional isomers). It has been shown that the compounds prepared are able to inhibit the growth of tumour cells. DE 3540952 describes 2-piperazino-pteridines which are substituted in the 6 position by a halogen atom selected from among a fluorine, chlorine or bromine atom. It has been shown that these compounds were able to inhibit the activity of tumour cells and human thrombocytes in vitro. DE 3323932 discloses 2-piperazino-pteridines which carry a dialkylamino, piperidino, morpholino, thiomorpholino or 1-oxidothiomorpholino group in the 4 position. It has been shown that these compounds were able to inhibit the activity of tumour cells and human thrombocytes in vitro. DE 3445298 describes pteridines with a large number of different substituents in the 2, 4, 6 and 7 position, while compounds with a 2-piperazino group on the pteridine skeleton are suitable as inhibitors of tumour growth and also have antithrombotic and metastasis-inhibiting properties. U.S. Pat. No. 2,940,972 discloses tri- and tetrasubstituted pteridine derivatives, commenting in general terms that these pteridines have valuable pharmacological properties, namely coronary artery dilating, sedative, antipyretic and analgesic activities.
The phosphodiesterase 4 inhibitors from the prior art are known to trigger side effects such as nausea and vomiting (Doherty, 1999, Curr. Op. Chem. Biol., Aug. 3, (4):466-73). The substances mentioned in this invention preferably inhibit the B-isoenzymes of phosphodiesterase 4 and therefore, are preferred PDE4B-inhibitors particularly suitable for treating the above-mentioned diseases. These are unlike other PDE4-inhibitors, which preferably inhibit other PDE4-isoenzymes (e.g. isoenzymes A, C or D), because they do not trigger side effects of nausea and vomiting in an animal model (S. Murinus, Yamamoto K. et al., Physiol. Behav., 2004, Oct. 30, 83(1), 151-6).
The aim of the present invention is to provide new compounds which are suitable for the prevention or treatment of respiratory or gastrointestinal complaints or diseases, inflammatory diseases of the joints, skin or eyes, diseases of the peripheral or central nervous system, or cancers, particularly those compounds which are characterized by reduced side effects, particularly emesis and nausea.